Renal electrolyte effects of guanylin and uroguanylin

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Abstract
Guanylin peptides are secreted from the intestine and influence electrolyte and water transport in intestine and kidney, suggesting that these peptides act as intestinal natriuretic peptides. This review presents recent research on renal guanylin and uroguanylin effects. After salty meals guanylin peptides are produced in the intestine activating anion secretion and inhibiting sodium absorption. In the kidney guanylin peptides induce saluresis and diuresis. The signaling of guanylin peptides in the intestine is well known, involving guanylate cyclase C and increases in cellular cGMP concentrations. As in the intestine in proximal tubule cells a cGMP and guanylate cyclase C-dependent signaling pathway exists. In guanylate cyclase C-deficient mice, renal effects are unaltered, which could be by explained by recently described new cGMP-independent signaling pathways. In proximal tubules, Uroguanylin activates a pertussis toxin-sensitive receptor. Another cGMP-independent signaling pathway of guanylin peptides involving phospholipase A2 and arachidonic acid is shown for principal cells of human and mouse cortical collecting ducts. Mechanisms and sites of renal actions of guanylin peptides are still not completely understood. Renal receptors for guanylin peptides are probably G-protein-coupled. The influences of guanylin peptides on natriuresis, kaliuresis, and diuresis are complex and only further detailed studies will allow a complete understanding of the function of these peptides.